Registration of SD-OCT en-face images with color fundus photographs based on local patch matching

Registration of multi-modal retinal images is very significant to integrate information gained from different modalities for a reliable diagnosis of retinal diseases by ophthalmologists. However, accurate image registration is a challenging, we propose an algorithm for registration of summed-voxel projection images (SVPIs) with color fundus photographs (CFPs) based on local patch matching. SVPIs are evenly split into 16 local image blocks for extracting matching point pairs by searching local maximization of the similarity function. These matching point pairs are used for a coarse registration and then a search region of feature matching points is redefined for a more accurate registration. The performance of our registration algorithm is tested on a series of datasets including 3 normal eyes and 20 eyes with age-related macular degeneration. The experiment demonstrates that the proposed method can achieve accurate registration results (the average of root mean square error is 128μm)

Comparability of automated drusen volume measurements in age-related macular degeneration: a MACUSTAR study report

Drusen are hallmarks of early and intermediate age-related macular degeneration (AMD) but their quantification remains a challenge. We compared automated drusen volume measurements between different OCT devices. We included 380 eyes from 200 individuals with bilateral intermediate (iAMD, n = 126), early (eAMD, n = 25) or no AMD (n = 49) from the MACUSTAR study. We assessed OCT scans from Cirrus (200 × 200 macular cube, 6 × 6 mm; Zeiss Meditec, CA) and Spectralis (20° × 20°, 25 B-scans; 30° × 25°, 241 B-scans; Heidelberg Engineering, Germany) devices. Sensitivity and specificity for drusen detection and differences between modalities were assessed with intra-class correlation coefficients (ICCs) and mean difference in a 5 mm diameter fovea-centered circle. Specificity was > 90% in the three modalities. In eAMD, we observed highest sensitivity in the denser Spectralis scan (68.1). The two different Spectralis modalities showed a significantly higher agreement in quantifying drusen volume in iAMD (ICC 0.993 [0.991–0.994]) than the dense Spectralis with Cirrus scan (ICC 0.807 [0.757–0.847]). Formulae for drusen volume conversion in iAMD between the two devices are provided. Automated drusen volume measures are not interchangeable between devices and softwares and need to be interpreted with the used imaging devices and software in mind. Accounting for systematic difference between methods increases comparability and conversion formulae are provided. Less dense scans did not affect drusen volume measurements in iAMD but decreased sensitivity for medium drusen in eAMD. Trial registration: ClinicalTrials.gov NCT03349801. Registered on 22 November 2017

Characteristics and Spatial Distribution of Structural Features in Age-Related Macular Degeneration: A MACUSTAR Study Report

Purpose: To report the prevalence and topographic distribution of structural characteristics in study participants with age-related macular degeneration (AMD) and controls in the cross-sectional study part of the MACUSTAR study (ClinicalTrials.gov Identifier: NCT03349801). Design: European, multicenter cohort study. Subjects: Overall, 301 eyes of 301 subjects with early (n = 34), intermediate (n = 168), and late AMD (n = 43), as well as eyes without any AMD features (n = 56). Methods: In study eyes with intermediate AMD (iAMD), the presence of structural AMD biomarkers, including pigmentary abnormalities (PAs), pigment epithelium detachment (PED), refractile deposits, reticular pseudodrusen (RPD), hyperreflective foci (HRF), incomplete/complete retinal pigment epithelium (RPE), and outer retinal atrophy (i/cRORA), and quiescent choroidal neovascularization (qCNV) was systematically determined in the prospectively acquired multimodal retinal imaging cross-sectional data set of MACUSTAR. Retinal layer thicknesses and the RPE drusen complex (RPEDC) volume were determined for the total study cohort in spectral-domain (SD) OCT imaging using a deep-learning–based algorithm. Main Outcome Measures: Prevalence and topographic distribution of structural iAMD features. Results: A total of 301 study eyes of 301 subjects with a mean (± standard deviation) age of 71.2 ± 7.20 years (63.1% women) were included. Besides large drusen, the most prevalent structural feature in iAMD study eyes were PA (57.1%), followed by HRF (51.8%) and RPD (22.0%). Pigment epithelium detachment lesions were observed in 4.8%, vitelliform lesions in 4.2%, refractile deposits in 3.0%, and qCNV in 2.4%. Direct precursor lesions for manifest retinal atrophy were detected in 10.7% (iRORA) and 4.2% (cRORA) in iAMD eyes. Overall, the highest RPEDC volume with a median of 98.92 × 10−4 mm³ was found in iAMD study eyes. Spatial analysis demonstrated a predominant distribution of RPD in the superior and temporal subfields at a foveal eccentricity of 1.5 to 2 mm, whereas HRF and large drusen had a distinct topographic distribution involving the foveal center. Conclusions: Detailed knowledge of the prevalence and distribution of structural iAMD biomarkers is vital to identify reliable outcome measure for disease progression. Longitudinal analyses are needed to evaluate their prognostic value for conversion to advanced disease stages. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references

Comparability of automated drusen volume measurements in age-related macular degeneration: a MACUSTAR study report

Drusen are hallmarks of early and intermediate age-related macular degeneration (AMD) but their quantification remains a challenge. We compared automated drusen volume measurements between different OCT devices. We included 380 eyes from 200 individuals with bilateral intermediate (iAMD, n = 126), early (eAMD, n = 25) or no AMD (n = 49) from the MACUSTAR study. We assessed OCT scans from Cirrus (200 × 200 macular cube, 6 × 6 mm; Zeiss Meditec, CA) and Spectralis (20° × 20°, 25 B-scans; 30° × 25°, 241 B-scans; Heidelberg Engineering, Germany) devices. Sensitivity and specificity for drusen detection and differences between modalities were assessed with intra-class correlation coefficients (ICCs) and mean difference in a 5 mm diameter fovea-centered circle. Specificity was > 90% in the three modalities. In eAMD, we observed highest sensitivity in the denser Spectralis scan (68.1). The two different Spectralis modalities showed a significantly higher agreement in quantifying drusen volume in iAMD (ICC 0.993 [0.991–0.994]) than the dense Spectralis with Cirrus scan (ICC 0.807 [0.757–0.847]). Formulae for drusen volume conversion in iAMD between the two devices are provided. Automated drusen volume measures are not interchangeable between devices and softwares and need to be interpreted with the used imaging devices and software in mind. Accounting for systematic difference between methods increases comparability and conversion formulae are provided. Less dense scans did not affect drusen volume measurements in iAMD but decreased sensitivity for medium drusen in eAMD

Retest variability and patient reliability indices of quantitative fundus autofluorescence in age-related macular degeneration: a MACUSTAR study report

This study aimed to determine the retest variability of quantitative fundus autofluorescence (QAF) in patients with and without age-related macular degeneration (AMD) and evaluate the predictive value of patient reliability indices on retest reliability. A total of 132 eyes from 68 patients were examined, including healthy individuals and those with various stages of AMD. Duplicate QAF imaging was conducted at baseline and 2 weeks later across six study sites. Intraclass correlation (ICC) analysis was used to evaluate the consistency of imaging, and mean opinion scores (MOS) of image quality were generated by two researchers. The contribution of MOS and other factors to retest variation was assessed using mixed-effect linear models. Additionally, a Random Forest Regressor was trained to evaluate the extent to which manual image grading of image quality could be replaced by automated assessment (inferred MOS). The results showed that ICC values were high for all QAF images, with slightly lower values in AMD-affected eyes. The average inter-day ICC was found to be 0.77 for QAF segments within the QAF8 ring and 0.74 for peripheral segments. Image quality was predicted with a mean absolute error of 0.27 on a 5-point scale, and of all evaluated reliability indices, MOS/inferred MOS proved most important. The findings suggest that QAF allows for reliable testing of autofluorescence levels at the posterior pole in patients with AMD in a multicenter, multioperator setting. Patient reliability indices could serve as eligibility criteria for clinical trials, helping identify patients with adequate retest reliability

Development and Valuation of a Preference-Weighted Measure in Age-Related Macular Degeneration From the Vision Impairment in Low Luminance Questionnaire—A MACUSTAR Report

Objectives: This study generates VILL-UI (Vision Impairment in Low Luminance - Utility Index), a preference-weighted measure (PWM) derived from the VILL-33 measure for use in patients with age-related macular degeneration (AMD) and valued to generate United Kingdom and German preference weights. Methods: A PWM consists of a classification system to describe health and utility values for every state described by the classification. The classification was derived using existing data collected as part of the MACUSTAR study, a low-interventional study on AMD, conducted at 20 clinical sites across Europe. Items were selected using psychometric and Rasch analyses, published criteria around PWM suitability, alongside instrument developer views and concept elicitation work that informed VILL-33 development. An online discrete choice experiment (DCE) with duration of the health state was conducted with the United Kingdom and German public. Responses were modeled to generate utility values for all possible health states. Results: The classification system has 5 items across the 3 domains of VILL-33: reading and accessing information, mobility and safety, and emotional well-being. The DCE samples (United Kingdom: n = 1004, Germany: n = 1008) are broadly representative and demonstrate good understanding of the tasks. The final DCE analyses produce logically consistent and significant coefficients. Conclusions: This study enables responses to VILL-33 to be directly used to inform economic evaluation in AMD. The elicitation of preferences from both United Kingdom and Germany enables greater application of VILL-UI for economic evaluation throughout Europe. VILL-UI fills a gap in AMD in which generic preference-weighted measures typically lack sensitivity